Novel direct curve comparison metrics for bioequivalence

The object of this work was to devise four new direct curve comparison (DCC) metrics and examine each metric's distribution properties and performance characteristics. DCC metrics, Cmax, and AUCi were calculated from two bioequivalence studies of three sustained release carbamazepine formulatio...

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Bibliographic Details
Published inPharmaceutical research Vol. 18; no. 6; pp. 734 - 741
Main Authors POLLI, James E, MCLEAN, Angus M
Format Journal Article
LanguageEnglish
Published New York, NY Springer 01.06.2001
Springer Nature B.V
Subjects
Anticonvulsants - blood
Anticonvulsants - pharmacokinetics
Area Under Curve
Biological and medical sciences
Carbamazepine - blood
Carbamazepine - pharmacokinetics
Confidence Intervals
Delayed-Action Preparations - pharmacokinetics
General pharmacology
Humans
Medical sciences
Models, Biological
Models, Chemical
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Therapeutic Equivalency
Bioequivalence
Anticonvulsant
Bioavailability
Tricyclic compound
In vitro
Carbamazepine
Absorption
Area under the curve
Dosage form
Active ingredient
Mathematical model
Pharmacokinetics
Dibenzazepine derivatives
Release
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Summary:The object of this work was to devise four new direct curve comparison (DCC) metrics and examine each metric's distribution properties and performance characteristics. DCC metrics, Cmax, and AUCi were calculated from two bioequivalence studies of three sustained release carbamazepine formulations, where a range of profile similarity was observed. DCC metric values and their confidence intervals were compared to Cmax and AUCi. The DCC metrics rho, rhom, deltaa, and deltas, exhibited more favorable distributions than Cmax and AUCi ratios, which were frequently skewed. The DCC metrics performed differently than Cmax and AUCi ratios in profile comparisons due to the nature of the DCC metrics. Unlike Cmax and AUCi, the DCC metrics utilize all data points to directly compare entire profiles. Each DCC metric appears to measure "exposure" in a single assessment. Possible bioequivalence acceptance criteria are: p < or =1.40, rhom, < or =0.35, deltaa, < or =0.27, and deltas < or =0.102. These DCC metrics, particularly rhom, are promising bioequivalence metrics for "exposure."
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0724-8741
1573-904X
DOI:10.1023/A:1011067908500